Despite immense efforts in behavioral interventions to promote safer sexual practices, sexually transmitted infections (STIs) continue to be a pandemic worldwide. Unfortunately, there are no effective vaccines or microbicides for the majority of STIs. A pathogen-specific, safe, effective and discreet vaginal microbicide that does not require daily or sex-associated dosing would provide a powerful prevention tool addressing the current gap in behavioral and pharmacological interventions. Among different classes of microbicide candidates currently in clinical and pre-clinical development, human monoclonal antibodies (mAb) delivered locally to mucosal surfaces offer exceptional promise combining safety, effectiveness and unparalleled specificity. Adding further to the promise of mAb, the Lai and Cone Labs recently discovered a novel antibody function in mucus - IgGs that trap individual pathogens in mucus - and have pioneered a technology enhancing the use of mAb in mucosal secretions based on carefully-tuned affinity between IgG-Fc and mucins, which will be exclusively licensed to Mucommune. We have shown that engineered mAb can trap Herpes viruses in human cervicovaginal mucus (CVM) with 10-fold greater potency than protection by neutralization. More importantly, trapping viruses in mucus with vaginally-dosed mAb can directly block vaginal Herpes transmission in vivo in the absence of other immune protective functions. The Lai Lab has since advanced this technology by showing that specific mAb trap not only viral but also highly motile bacterial pathogens, and that pathogen trapping can occur in lung and GI mucus secretions, underscoring the universal nature of this novel IgG-mucin function and the broad applicability of the Mucommune technology. In this Phase I STTR, we will build upon our work to demonstrate that pathogen-trapping mAb, when formulated into sustained release polymeric capsules, will remain sufficiently stable upon long term exposure to human mucus secretions and retain its pathogen-trapping function (i.e. both pathogen- and mucin- binding) when released into CVM over a 35 day period. In Aim 1, we will encapsulate pathogen-trapping mAb into polymeric capsules prepared from 3D printing, and characterize the integrity of the mAb before/after loading and after release from the polymeric capsules. In Aim 2, we will incubate mAb-loaded capsules with human CVM, and measure the stability and pathogen trapping potency of encapsulated and released mAb in CVM. Successful completion of these studies will lead to a Phase II proposal, where the overall goal will be to develop a shelf-stable vaginal ring with embedded polymeric capsules that slowly release a cocktail of mAb, providing effective protection against a broad spectrum of STIs with convenient, once a month application. By enabling enhanced mAb function in mucus secretions, we expect Mucommune will help pave the way for improved, molecularly-targeted therapies and prophylaxis against a broad spectrum of pathogens and microbes across all major mucosal surfaces.